Diabetes mellitus is associated with a group of major complications, which involve the heart, the kidney, the eyes and the nervous system. These several complications are thought to involve basic abnormalities of the small and large blood vessels which supply nutrients to the affected organs and hence partly control their metabolism. The mechanism whereby diabetes mellitus results in the vascular abnormalities is basically unknown. We have recently found that the cells lining all blood vessels, the endothelial cells, possess highly specific areas on their surface which recognize and bind insulin. In the present proposal, we plan to assess the effects of insulin and insulin-like growth peptides (IGF) on endothelial cell function. We will evaluate the interactions of insulin and IFS with specific surface receptors on endothelial cells and also determine their effects on specific endothelial cell functions.